The Unviersity of California, San Diego is committed to developing in-vivo imaging at the molecular and cellular level to answer basic molecular biology questions, to determine the molecular basis of drug action, interaction and resistance, to assess the effect of therapeutic interventions and to probe unique animal models at the molecular level of disease in general, and cancer in particular. The ultimate goal is to develop new diagnostic and therapeutic tools to detect and distinguish aggressive from indolent lesions in order to treat patients at the early stages of cancer development. Also critical is to assess therapeutic effects when therapy is directed at molecular targets such as enzyme inhibition or interference with specific pathways. The centralized space in the new Moores UCSD Cancer Center (MCC) that also houses our rodent imaging facility adjacent to the vivarium will group the ICMIC team with other cancer investigators. We have built the ICMIC along side the NCI funded NanoTumor Center within the MCC to maximize efficiency and synergism. The P20 award 5 years ago began our multidisciplinary collaboration. Over the last five years we have submitted more than 10 new ideas as R01-type projects in the P50s and many development projects in the P20 and P50 submissions. Eight of those ideas (7 for projects and 1 developmental project) have now been funded by the NIH, DOD, or DOE. We present here 5 new projects and one that was submitted previously that has been revised. The projects submitted in this P50 application focus on the interface between imaging and therapy. Project 1 aims to detect matrix metalloproteinase in tumors, a sign of tumor aggressiveness, with ultrasound contrast agents. They plan to take advantage of the fact that fluorocarbon emulsions are visible only when combined to induce aggregation at the time the emulsion is exposed to the enzyme of interest. Project 2 aims to label a platinum carrying polymer for PET and SPECT imaging of a cancer chemotherapeutic currently in clinical trial. Their goal is to provide the clinicians with drug kinetics and propose to increase the agent's therapeutic index by targeting it as the vitamin B-12 receptor. Project 3 proposes a clever nanoparticle self-assembly system to target angiogenesis, also a sign of tumor aggressiveness, for imaging and therapy. The Developmental Projects represent cutting edge research that focus on cell labeling, gene delivery, and optical imaging of stem cell cancers. We also focus this ICMIC on Career Development and present three applicants for training in molecular imaging. The P.l.s of one major project and all 3 Developmental Projects are junior faculty from Pathology (1), Medicine (3) and the Cancer Center (1) that are mentored by seasoned investigators. The Institutional support is significant. We have been provided prime space in the cancer center, all rodent imaging equipment are located in the cancer center adjacent to the vivarium, and key personnel.